Increased serum methylmalonic acid levels were associated with the presence of cognitive dysfunction in older chronic kidney disease patients with albuminuria.

BACKGROUND: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). METHODS: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. RESULTS: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. CONCLUSION: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Urotensin II can Induce Skeletal Muscle Atrophy Associated with Upregulating Ubiquitin-Proteasome System and Inhibiting the Differentiation of Satellite Cells in CRF Mice.

Skeletal muscle wasting and atrophy is highly prevalent in chronic renal failure (CRF) and increases the risk of mortality. According to our previous study, we speculate that urotensin II (UII) can induce skeletal muscle atrophy by upregulating ubiquitin-proteasome system(UPS) in CRF. C2C12 mouse myoblast cells were differentiated into myotubes, and myotubes were exposed to different concentrations of UII. Myotube diameters, myosin heavy chain(MHC), p-Fxo03A, skeletal muscle-specific E3 ubiquitin ligases such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1) were detected. Three animal models (the sham operation mice as normal control (NC) group, wild-type C57BL/6 mice with 5/6 nephrectomy (WT CRF) group, UII receptor gene knock out (UT KO) mice with 5/6 nephrectomy (UT KO CRF) group) were designed. Cross-sectional area (CSA) of skeletal muscle tissues in three animal models were measured, and western blot detected protein of UII, p-Fxo03A, MAFbx and MuRF1, and immunofluorescence assays explored the satellite cell marker of Myod1 and Pax7, and PCR arrays detected the muscle protein degradation genes, protein synthesis genes and the genes which were involved in muscle components. UII could decrease mouse myotube diameters, and upregulate dephosphorylated Fxo03A protein. MAFbx and MuRF1 were higher in WT CRF group than that in NC group, but after UII receptor gene was knocked out (UT KO CRF), their expressions were downregulated. UII could inhibit the expression of Myod1 but not Pax7 in animal study. We first demonstrate that skeletal muscle atrophy induced by UII associated with upregulating ubiquitin-proteasome system and inhibiting the differentiation of satellite cells in CRF mice.

Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease.

INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1ß was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1ß release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients.

Expression of urotensin II is positively correlated with pyroptosis-related molecules in patients with severe preeclampsia.

Purpose: We studied the expression of urotensin II (UII) and its relationships with markers of pyroptosis in preeclampsia. Methods: 48 pregnant subjects were recruited consisting of 28 severe preeclampsia pregnancies (SPE) and 20 healthy pregnancies. We detected expressions of UII and markers of pyroptosis such as NLR-family pyrin domain (PYD)-containing 3 (NLRP-3), caspase-1/4/5, interleukin-1ß (IL-1ß), and gasdermin D (GSDMD) in placentas of patients with SPE and healthy pregnancies. Results: SPE group have higher expression of UII and NLRP-3, caspase-1, interleukin-1ß (IL-1ß), and GSDMD than that normal controls by IHC, real-time PCR, and western blot. IHC analysis manifests that the expressions of UII and pyroptosis-related molecules are mainly located in the placental cytotrophoblasts. Expressions of UII mRNA and protein are significantly positively correlated with pyroptosis marker such as NLRP3, caspase-1, GSDMD mRNA and protein by Pearson correlation analysis. Moreover, UII, NLRP-3, caspase-1, interleukin-1ß (IL-1ß), and GSDMD are positively related with systolic blood pressure, meanwhile caspase-1 and GSDMD are positively correlated with urine protein in SPE patients. We firstly verify that UII has a positive correlation with pyroptosis markers in placentas of preeclampsia patients; besides, pyroptosis-related proteins are positively correlated with systolic blood pressure and urine protein in patients with severe preeclampsia.

Urotensin II Induces Mice Skeletal Muscle Atrophy Associated with Enhanced Autophagy and Inhibited Irisin Precursor (Fibronectin Type III Domain Containing 5) Expression in Chronic Renal Failure.

BACKGROUND/AIMS: Skeletal muscle atrophy is one of the main manifestations of protein energy wasting. We hypothesized that urotensin II (UII) can lead to skeletal muscle atrophy through upregulating autophagy and affecting Irisin precursor fibronectin type III domain containing 5 (FNDC5) expressions. METHODS: Three animal models (the sham operation, wild-type C57BL/6 mice with 5/6 nephrectomy, UII receptor (UT) gene knockout (UTKO) mice with 5/6 nephrectomy) were designed. Skeletal muscle weight, cross-sectional area (CSA) along with UII, FNDC5, LC3, and p62 expression were investigated. C2C12 cells were differentiated for up to 4 days into myotubes. These cells were then exposed to different UII concentrations (10-5 to 10-7 M) for 6-12 h and analyzed for the expressions of autophagic markers. These cells were also exposed to the same predetermined UII concentrations for 48-72 h and analyzed for the FNDC5 expression. Myotube diameter was measured. RESULTS: Upregulation of UII expression in skeletal muscle tissue was accompanied by reduced muscle weight and skeletal muscle CSA in the 2 posterior limbs, upregulated autophagy markers expression, and downregulated FNDC5 expression in 5/6 nephrectomy mice. The decrease of skeletal muscle weight, skeletal muscle CSA, downregulation of FNDC5 expression, and the upregulation of autophagy markers were inhibited in UTKO with 5/6 nephrectomy mice. Our in vitrostudy showed that UII could directly decrease myotube diameter, induce autophagy markers upregulation, and inhibit expression of FNDC5. When UII receptor gene was interfered by UT-specific siRNA, UII induced autophagy markers upregulation and FNDC5 downregulation were inhibited. CONCLUSION: We are the first to verify UII induces mice skeletal muscle atrophy associated with enhanced skeletal muscle autophagy and inhibited FNDC5 expression in chronic renal failure.

The Efficacy of Mesenchymal Stem Cells for Cardiomyopathy: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of mesenchymal stem cells (MSCs) for cardiomyopathy remains controversial. We conducted a systematic review and meta-analysis to explore the influence of MSCs versus placebo on the treatment efficacy of cardiomyopathy. METHODS: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through November 2018 for randomized controlled trials (RCTs) assessing the treatment efficacy of MSCs versus placebo for cardiomyopathy. This meta-analysis was performed using the random-effect model. RESULTS: Five RCTs were included in the meta-analysis. Overall, compared with the control group for cardiomyopathy, MSCs treatment showed significantly positive effect on LVEF (MD = 5.85; 95% CI = 3.88 to 7.83; P < .00001), NYHA classification (MD = -1.11; 95% CI = -1.45 to -0.77; P < .00001), LVEDd (MD = -3.00; 95% CI = -5.37 to -0.64; P = .01), and the proportion of fixed defects (MD = -4.22; 95% CI = -6.91 to -1.52; P = .002), but had no obvious influence on death (RR = 0.42; 95% CI = 0.12 to 1.50; P = 0.18) or adverse events (RR = 1.14; 95% CI = 0.70 to 1.86; P = .59). CONCLUSION: MSCs treatment showed favorable impact on LVEF, NYHA classification, LVEDd, and the proportion of fixed defects for cardiomyopathy patients.

3D-DNA walking nanomachine based on catalytic hairpin assembly and copper nanoclusters for sensitive detection of hepatitis C virus.

Rapid and accurate detection of the hepatitis C virus (HCV) is essential for early diagnosis and prevention of virus transmission. This study presents a novel approach that combines the three-dimensional (3D)-DNA walking nanomachine with catalytic hairpin assembly (CHA) and copper nanoclusters (CuNCs). By integrating CHA with the 3D DNA walking nanomachine, efficient target amplification on 3D surfaces was achieved, leading to improved reaction speed and detection performance. Terminal deoxynucleotidyl transferase (TdT) was utilized to generate T-rich DNA sequences. These sequences served as templates for the formation of CuNCs, which functioned as the readout signal. The optimized 3D-DNA walking nanomachine exhibited excellent sensitivity in detecting HCV, with a detection limit of 42.4 pM and a linear range of 100 pM to 2 nM. The biosensor demonstrated excellent selectivity and reproducibility, with a recovery rate ranging from 94% to 108% for the detection of real samples. This design holds great potential for sensitive, label-free, and reliable detection of HCV in clinical settings. Furthermore, the versatility of this approach allows for the customization of target sequences, thereby facilitating the detection of various nucleic acid targets. Therefore, this method has the potential to advance personalized medicine, disease management, and genetic analysis in the field of molecular diagnosis.

Prevalence of cognitive impairment and its predictors among chronic kidney disease patients: A systematic review and meta-analysis.

BACKGROUND: Cognitive impairment (CI) is common among patients with chronic kidney disease (CKD), and is associated with a poor prognosis. We assessed the prevalence and associated factors of CI in patients with CKD. METHODS: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and the Web of Science through December 1, 2023. Random effects models were performed with subgroup analyses to further explore the heterogeneity. RESULTS: 50 studies involving 25,289 CKD patients were included. The overall prevalence of CI was 40% (95% confidence interval 33-46). The pooled prevalence of CI was relatively higher in CKD patients from Africa (58%), Asia (44%) and America (37%). Attention and executive dysfunction appeared to be the most common manifestations. The prevalence of CI was higher among patients with hemodialysis (53%) and peritoneal dialysis (39%) than those without dialysis (32%) and post-kidney transplanted (26%). In addition, advanced age, the presence of diabetes and hypertension might increase the risk of CI in CKD patients. CONCLUSIONS: People with CKD have a high prevalence of CI, especially in patients with hemodialysis. An early and comprehensive screening for CI in CKD patients is needed to improve clinical outcomes. TRIAL REGISTRATION: Registration number: PROSPERO (CRD42023412864).

Orientin suppresses osteoclastogenesis and ameliorates ovariectomy-induced osteoporosis via suppressing ROS production.

The aberrant differentiation of osteoclasts is a key feature of the pathogenesis of osteoporosis, which has a devastating impact on human health. While the effects of Orientin (Ori) on osteoporosis, particularly on RANKL-stimulated osteoclast production and activation, remain still unclear, Ori has been found to display several biological activities, including antioxidant and anti-inflammatory. In this work, we investigated the possible pathways through which Ori suppressed RANKL-induced osteoclast development and showed for the first time that it does so. The macrophages from the bone marrow (BMMs) were cultivated and then treated with Ori after being stimulated with RANKL. Then, TRAP-positive multinucleated cells were counted, and F-actin ring analysis was used to assess Ori's impact on mature osteoclast development. In addition, dihydroethidium (DHE) staining was used to evaluate the impact of Ori on RANKL-induced reactive oxygen species (ROS). In addition, we performed western blotting and quantitative RT-PCR analysis to investigate probable causes of these downregulation effects. We discovered that Ori inhibits the creation of osteoclasts, the gene and protein expressions unique to osteoclasts, and the ROS production. By activating Nrf2 and other ROS-scavenging enzymes, Ori reduces intracellular ROS levels. The expression of the main transcription factor of osteoclast development, c-Fos, was downregulated together with NFATc1, CTSK, and NFATc2, thanks to Ori's inhibition of RANKL-induced NF-κB. Consistent with its in vitro antiosteoclastogenic action, Ori therapy in the ovariectomized (OVX) rat model was also able to restore bone mass and improve microarchitecture in the distal femurs. Together, our results demonstrate that Ori is a flavonoid molecule with therapeutic promise for bone illnesses associated with osteoclasts, such as osteoporosis.

Serum irisin level is higher in peritoneal dialysis than in hemodialysis.

BACKGROUND: Previous studies have proved that irisin is related to the development of chronic kidney disease. In this study, we aimed to compare serum irisin level in patients treated with peritoneal dialysis (PD) and hemodialysis (HD). METHODS: Two hundred and fifty-two dialysis patients (146 PD patients and 106 HD patients) were included in the study. Levels of serum irisin and other parameters were compared between the two groups' patients. RESULTS: There were higher serum irisin levels in PD patients than those in HD patients [113.10 (106.15 ~ 119.15) ng/ml vs. 45.72(21.67 ~ 79.71) ng/ml, P < 0.001]. Moreover, body fat mass, percent body fat, serum calcium, high-density lipoprotein, low-density lipoprotein, carbon dioxide combining power (CO2CP) and residual renal function were higher in patients on PD than that in those on HD, whereas levels of lean body mass, systolic blood pressure, albumin, serum uric acid, potassium, and phosphorus（It should be "were" replace are) are higher in HD patients in comparison to PD patients. Dialysis modality (PD/HD), serum CO2CP level, lean body mass, and percent body fat independently positively correlated with natural logarithm of irisin (lnirisin) by multivariate linear regression analysis. CONCLUSIONS: In this study, we prove that serum irisin level is significantly higher in patients treated with peritoneal dialysis than that with hemodialysis. As well as, increasing skeletal muscle mass and fat body percent, and correcting metabolic acidosis may increase serum irisin levels.

Infectious Disease Diagnosis and Pathogen Identification Platform Based on Multiplex Recombinase Polymerase Amplification-Assisted CRISPR-Cas12a System.

Controlling and mitigating infectious diseases caused by multiple pathogens or pathogens with several subtypes require multiplex nucleic acid detection platforms that can detect several target genes rapidly, specifically, sensitively, and simultaneously. Here, we develop a detection platform, termed Multiplex Assay of RPA and Collateral Effect of Cas12a-based System (MARPLES), based on multiplex nucleic acid amplification and Cas12a ssDNase activation to diagnose these diseases and identify their pathogens. We use the clinical specimens of hand, foot, and mouth disease (HFMD) and influenza A to evaluate the feasibility of MARPLES in diagnosing the disease and identifying the pathogen, respectively, and find that MARPLES can accurately diagnose the HFMD associated with enterovirus 71, coxsackievirus A16 (CVA16), CVA6, or CVA10 and identify the exact types of H1N1 and H3N2 in an hour, showing high sensitivity and specificity and 100% predictive agreement with qRT-PCR. Collectively, our findings demonstrate that MARPLES is a promising multiplex nucleic acid detection platform for disease diagnosis and pathogen identification.

Vegetation coverage change and associated driving forces in mountain areas of Northwestern Yunnan, China using RS and GIS.

The dynamics of vegetation coverage and associated driving forces are one of the key issues in global environmental change. In the study, taking Lijiang County as a case, the Normalized Difference Vegetation Index was used to quantify vegetation coverage change in mountain areas of Northwestern Yunnan, China, with the application of remote sensing data and GIS technologies. And associated driving forces of vegetation coverage change were also analyzed, with a focus on land use change and elevation. The results showed that there was high vegetation coverage with a significant increase in the whole county during 1986-2002. However, due to economic development and the implementation of environmental protection polices, vegetation coverage change in the county showed distinct spatial diversity, which mainly behaved as the increasing in the northwest of the county with low human activities, and the decreasing in the south with high economic development. The results also showed that as a restrictive factor, elevation was of great signification on the spatial distribution of vegetation coverage in a broad scale; while in the county level, it was land use that determined the vegetation coverage, since the change of vegetation coverage grades in the study area was mainly associated with the change of land use types.

Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease.

Irisin protects the cardiovascular system against vascular diseases. However, its role in chronic kidney disease (CKD) -associated vascular calcification (VC) and the underlying mechanisms remain unclear. In the present study, we investigated the potential link among Irisin, pyroptosis, and VC under CKD conditions. During mouse vascular smooth muscle cell (VSMC) calcification induced by ß-glycerophosphate (ß-GP), the pyroptosis level was increased, as evidenced by the upregulated expression of pyroptosis-related proteins (cleaved CASP1, GSDMD-N, and IL1B) and pyroptotic cell death (increased numbers of PI-positive cells and LDH release). Reducing the pyroptosis levels by a CASP1 inhibitor remarkably decreased calcium deposition in ß-GP-treated VSMCs. Further experiments revealed that the pyroptosis pathway was activated by excessive reactive oxygen species (ROS) production and subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in calcified VSMCs. Importantly, Irisin effectively inhibited ß-GP-induced calcium deposition in VSMCs in vitro and in mice aortic rings ex vivo. Overexpression of Nlrp3 attenuated the suppressive effect of Irisin on VSMC calcification. In addition, Irisin could induce autophagy and restore autophagic flux in calcified VSMCs. Adding the autophagy inhibitor 3-methyladenine or chloroquine attenuated the inhibitory effect of Irisin on ß-GP-induced ROS production, NLRP3 inflammasome activation, pyroptosis, and calcification in VSMCs. Finally, our in vivo study showed that Irisin treatment promoted autophagy, downregulated ROS level and thereby suppressed pyroptosis and medial calcification in aortic tissues of adenine-induced CKD mice. Together, our findings for the first time demonstrated that Irisin protected against VC via inducing autophagy and inhibiting VSMC pyroptosis in CKD, and Irisin might serve as an effective therapeutic agent for CKD-associated VC.

Irisin alleviates vascular calcification by inhibiting VSMC osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling pathway in chronic kidney disease.

BACKGROUND AND AIMS: Vascular calcification (VC) is an intricate active process, significantly controlled by vascular smooth muscle cells (VSMCs). Mitochondrial dysfunction plays a pivotal role in VC and VSMCs osteoblastic transformation. We previously reported that decreased levels of Irisin were independently associated with VC in hemodialysis patients. The present study aimed to investigate the role of Irisin in VC, especially in VSMCs osteoblastic transformation and mitochondrial function. METHODS: In vitro, VSMCs calcification was induced by ß-glycerophosphate, while in vivo VC was triggered by adenine and high phosphorus diet. Alizarin red, Von Kossa staining, and calcium and Alp activity were performed to test VC. Western blot and immunohistochemical staining were employed to analyze the expression of proteins associated with VSMCs osteoblastic transformation and AMPK signaling. Mitochondrial membrane potential (MMP) and structures were observed by immunofluorescence staining. RESULTS: Irisin alleviated VSMCs calcification induced by ß-glycerophosphate. Mechanistically, Irisin activated AMPK and downregulated the expression of Drp1, further alleviating mitochondria fission and VSMCs osteoblastic transformation. In vivo, Irisin decreased serum creatinine, urea and phosphorous levels in chronic kidney disease (CKD) mice. Importantly, Irisin treatment postponed CKD-associated VC with the upregulation of α-Sma and p-AMPK expression, and the downregulation of Runx2 and Drp1 expression. CONCLUSIONS: Our results firstly reveal that Irisin inhibits CKD-associated VC. Irisin suppresses VSMCs osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling.

A Chinese Patent Medicine JiaYanKangTai Alleviates Inflammatory Lesions of Experimental Autoimmune Thyroiditis by Regulating Interleukin-17 Signaling.

Objective: This study was aimed to investigate the effects of JiaYanKangTai (JYKT) on regulating interleukin-17 (IL-17) signaling in rats with autoimmune thyroiditis. Methods: Lewis rats were administrated with JYKT for eight weeks after a seven-week subcutaneous injection of thyroglobulin with adjuvant and feeding iodine water. Ultrasonography was performed and total volume of thyroid was calculated. The expressions of autoantibodies and hormones were detected. Morphological changes of thyroid were observed. Metabolomics profile and metabolic network analysis were conducted. IL-17 signaling was detected by polymerase chain reaction and immunohistochemistry separately. Results: JYKT reduced the mean volumes of thyroid, decreased both levels of TPOAb and TGAb, and alleviated lymphocytic infiltration of the thyroid. Metabolic network analysis of metabolomics proved IL-17 signaling pathway as a critical pathway in JYKT administration for autoimmune thyroiditis. JYKT downregulated expressions of IL-17A, TRAF6, p-ERK1/2 and TNF-α. Conclusion: JYKT alleviated inflammatory lesions of experimental autoimmune thyroiditis by regulating IL-17 signaling.

Mixed Tree Nut Snacks Compared to Refined Carbohydrate Snacks Resulted in Weight Loss and Increased Satiety during Both Weight Loss and Weight Maintenance: A 24-Week Randomized Controlled Trial.

Mixed tree nuts (MTNs) are an excellent source of protein and healthy fat contributing to satiety. However, their relatively high caloric content might not be beneficial in a weight loss diet. The present study was designed to test whether including MTNs in a weight loss and maintenance program interferes with weight management compared to a refined carbohydrate pretzel snack (PS). We performed a randomized, controlled, two-arm study in 95 overweight individuals consuming 1.5 oz of MTNs or PS daily as part of a hypocaloric weight loss diet (-500 kcal) over 12 weeks followed by an isocaloric weight maintenance program for 12 weeks. Participants in both groups experienced significant weight loss (12 weeks: -1.6 and -1.9 and 24 weeks: -1.5 and -1.4 kg) compared to baseline in the MTN and PS groups, respectively. However, there was no difference in weight loss and other outcome parameters between the MTN and PS groups. The MTN group showed a significant increase in satiety at 24 weeks. Both groups had a decrease in diastolic blood pressure at 12 weeks. Participants in the MTN group showed significant decreases in heart rate at 4, 12, and 24 weeks. Plasma oleic acid was significantly increased at 12 and 24 weeks in the MTN group but only at 12 weeks in the PS group. Plasma MCP-1 was decreased significantly in the MTN group at 4 weeks. In summary, participants in both groups lost weight, but only the MTN intervention increased satiety at 24 weeks, enhanced retention, decreased heart rate, and increased serum oleic acid at 24 weeks.

The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

Role of MnO2 in controlling iron and arsenic mobilization from illuminated flooded arsenic-enriched soils.

This study examined the role of intermittent illumination/dark conditions coupled with MnO2-ammendments to regulate the mobility of As and Fe in flooded arsenic-enriched soils. Addition of MnO2 particles with intermittent illumination led to a pronounced increase in the reductive-dissolution of Fe(III) and As(V) from flooded soils compared to a corresponding dark treatments. A higher MnO2 dosage (0.10 vs 0.02 g) demonstrated a greater effect. Over a 49-day incubation, maximum Fe concentrations mobilized from the flooded soils amended with 0.10 and 0.02 g MnO2 particles were 2.39 and 1.85-fold higher than for non-amended soils under dark conditions. The corresponding maximum amounts of mobilized As were at least 92 % and 65 % higher than for non-amended soils under dark conditions, respectively. Scavenging of excited holes by soil humic/fulvic compounds increased mineral photoelectron production and boosted Fe(III)/As(V) reduction in MnO2-amended, illuminated soils. Additionally, MnO2 amendments shifted soil microbial community structure by enriching metal-reducing bacteria (e.g., Anaeromyxobacter, Bacillus and Geobacter) and increasing c-type cytochrome production. This microbial diversity response to MnO2 amendment facilitated direct contact extracellular electron transfer processes, which further enhanced Fe/As reduction. Subsequently, the mobility of released Fe(II) and As(III) was partially attenuated by adsorption, oxidation, complexation and/or coprecipitation on active sites generated on MnO2 surfaces during MnO2 dissolution. These results illustrated the impact of a semiconducting MnO2 mineral in regulating the biogeochemical cycles of As/Fe in soil and demonstrated the potential for MnO2-based bioremediation strategies for arsenic-polluted soils.

Prediction of the mechanisms of action of Shenkang in chronic kidney disease: A network pharmacology study and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine provides a unique curative treatment of complex chronic diseases, including chronic kidney disease (CKD), which is not effectively treated with the current therapies. The pharmacological mechanisms of Shenkang (SK), a herbal medicine containing rhubarb (Rheum palmatum L. or R. tanguticum Maxim. ex Balf.), red sage (Salvia miltiorrhiza Bunge), safflower (Carthamus tinctorius L.), and astragalus (Astragalus mongholicus Bunge), widely used to treat CKD in China, are still unclear. AIM OF THE STUDY: In this study, the comprehensive approach used for elucidating the pharmacological mechanisms of SK included the identification of the effective constituents, target prediction and network analysis, by investigating the interacting pathways between these molecules in the context of CKD. These results were validated by performing an in vivo study and by comparison with literature reviews. MATERIALS AND METHODS: This approach involved the following main steps: first, we constructed a molecular database for SK and screened for active molecules by conducting drug-likeness and drug half-life evaluations; second, we used a weighted ensemble similarity drug-targeting model to accurately identify the direct drug targets of the bioactive constituents; third, we constructed compound-target, target-pathway, and target-disease networks using the Cytoscape 3.2 software and determined the distribution of the targets in tissues and organs according to the BioGPS database. Finally, the resulting drug-target mechanisms were compared with those proposed by previous research on SK and validated in a mouse model of CKD. RESULTS: By using Network analysis, 88 potential bioactive compounds in the four component herbs of SK and 85 CKD-related targets were identified, including pathways that involve the nuclear factor-κB, mitogen-activated protein kinase, transient receptor potential, and vascular endothelial growth factor, which were categorized as inflammation, proliferation, migration, and permeability modules. The results also included different tissues (kidneys, liver, lungs, and heart) and different disease types (urogenital, metabolic, endocrine, cardiovascular, and immune diseases as well as pathological processes) closely related to CKD. These findings agreed with those reported in the literature. However, our findings with the network pharmacology prediction did not account for all the effects reported for SK found in the literature, such as regulation of the hemodynamics, inhibition of oxidative stress and apoptosis, and the involvement of the transforming growth factor-ß/SMAD3, sirtuin/forkhead box protein O (SIRT/FOXO) and B-cell lymphoma-2-associated X protein pathways. The in vivo validation experiment revealed that SK ameliorated CKD through antifibrosis and anti-inflammatory effects, by downregulating the levels of vascular cell adhesion protein 1, vitamin D receptor, cyclooxygenase-2, and matrix metalloproteinase 9 proteins in the unilateral ureteral obstruction mouse model. This was consistent with the predicted target and pathway networks. CONCLUSIONS: SK exerted a curative effect on CKD and CKD-related diseases by targeting different organs, regulating inflammation and proliferation processes, and inhibiting abnormal extracellular matrix accumulation. Thus, pharmacological network analysis with in vivo validation explained the potential effects and mechanisms of SK in the treatment of CKD. However, these findings need to be further confirmed with clinical studies.

Acute Effects of Cinnamon Spice on Post-prandial Glucose and Insulin in Normal Weight and Overweight/Obese Subjects: A Pilot Study.

Clinical studies and meta-analyses have supported the notion that consuming cinnamon spice long term can have beneficial effects in individuals with normal glucose homeostasis and varying degrees of glucose intolerance including type 2 diabetes. The objective of this study was to evaluate the acute effect of cinnamon on the post-prandial responses to a typical American breakfast in normal and overweight/obese participants (ClinicalTrials.gov registration No. NCT04686552). The consumption of a single dose of 6 g of cinnamon added to oatmeal prepared with milk resulted in a significant reduction of one of our primary outcomes post-prandial insulin response (niAUC0-180min) in overweight/obese participants compared to control consuming breakfast without cinnamon. We also performed exploratory analysis of secondary outcomes. In normal weight participants, we observed a decrease of post-prandial glucagon response (niAUC0-180min and glucagon levels at 60-120 min) and C-peptide response (30 min) comparing breakfast with to without cinnamon. Cinnamon consumption did not change post-prandial glycemic response in normal weight participants, but increased 60 min post-prandial glucose in overweight/obese participants compared to control. In summary, cinnamon consumption differentially affected post-prandial hormonal responses in normal and overweight/obese participants.